Point-of-care diagnostic technology in paediatric ambulatory care: a qualitative interview study of English clinicians and stakeholders.

Point-of-care (POC) tests have the potential to improve paediatric healthcare. However, both the development and evaluation of POC technology have almost solely been focused on adults. We aimed to explore frontline clinicians' and stakeholders' current experience of POC diagnostic technology in children in England; and to identify areas of unmet need. DESIGN, SETTING AND PARTICIPANTS: Qualitative semistructured telephone interviews were carried out with purposively sampled participants from clinical paediatric ambulatory care and charity, industry and policymaking stakeholders. The interviews were audio-recorded, transcribed and analysed thematically. RESULTS: We interviewed 19 clinicians and 8 stakeholders. The main perceived benefits of POC tests and technologies were that they aided early decision-making and could be convenient and empowering when used independently by patients and families. Clinicians and stakeholders wanted more POC tests to be available for use in clinical practice. Most recognised that play and reward are important components of successful POC tests for children. Clinicians wanted tests to give them answers, which would result in a change in their clinical management. Detecting acute serious illness, notably distinguishing viral and bacterial infection, was perceived to be an area where tests could add value. POC tests were thought to be particularly useful for children presenting atypically, where diagnosis was more challenging, such as those less able to communicate, and for rare serious diseases. Many participants felt they could be useful in managing chronic disease. CONCLUSIONS: This exploratory study found that clinicians and stakeholders supported the use of diagnostic POC technology in paediatric ambulatory care settings in England. Some existing tests are not fit for purpose and could be refined. Industry should be encouraged to develop new child-friendly tests tackling areas of unmet need, guided by the preferred characteristics of those working on the ground.

Primary care preparedness for the SARS-CoV-2 pandemic: a survey of NHS GPs.

BACKGROUND: Primary care manages a significant proportion of healthcare in the United Kingdom and should be a key part of the SARS-CoV-2 pandemic response. AIM: To assess preparedness for the SARS-CoV-2 pandemic by understanding GPs' perception of their ability to manage current and future service demand, set-up of triage processes, and training in Covid-19 infection prevention and control procedures. DESIGN AND SETTING: Cross-sectional survey of practicing GPs in the United Kingdom, with 2 rounds of data collection early in the pandemic. METHODS: Online survey, scripted and hosted by medeConnect Healthcare, comprising 6 closed prompts on 7-point Likert scales, and an optional free-text component. Quantitative data were analysed using descriptive statistics. Free-text data were analysed thematically. RESULTS: One thousand two GPs completed each round; 51 GPs completed free-text responses in March, and 64 in April. Quantitative data showed greatest confidence in triage of Covid-19 patients, and GPs were more confident managing current than future Covid-19 demand. GPs' responses were more optimistic and aligned in April than March. Free-text data highlighted that GPs were concerned about lack of appropriate personal protective equipment and personal risk of Covid-19 infection in March, and unmet needs of non-Covid-19 patients in April. In both rounds, GPs expressed feeling overlooked by government and public health bodies. CONCLUSION: Guidance to support general practice clinicians to manage future waves of Covid-19 or other health emergencies must be tailored to general practice from the outset, to support clinicians to manage competing health demands, and mitigate impacts on primary care providers' wellbeing.

The SARS-CoV-2 pandemic has posed significant challenges for the health services in the United Kingdom and abroad. A Doctors Association UK poll published in early March 2020 found that only 1% of 800 GPs believed the NHS was well prepared for the SARS-CoV-2 pandemic. We surveyed 1,002 GPs across the United Kingdom to gauge how well prepared they felt to cope with the challenges posed by Covid-19. We conducted surveys in March and April 2020, an important time early in the pandemic with rapid changes and uncertainty. We found that GPs were more confident about their ability to manage Covid-19 patients, and do so safely, in April. GPs were most confident that they would be able to triage Covid-19 patients but were concerned about future Covid-19 demand. GPs expressed frustration about a lack of personal protective equipment in March. In April, GPs' primary concern was that patients with other health concerns were not being seen. In both samples, GPs expressed feelings of being overlooked by the government. Primary care needs tailored guidance from as early as possible in a health crisis to support clinicians to manage the competing demands of responding to emergency situations, maintain usual care and their own wellbeing.

Adenovirus vectors activate Vδ2+ γδT cells in a type I interferon-, TNF-, and IL-18-dependent manner.

Vδ2+ γδT cells are unconventional T cells that can be activated by cytokines without TCR signaling. Adenovirus vaccine vectors activated Vδ2+ γδT cells in an interleukin 18-, TNF-, and type I interferon-dependent manner. This stimulatory capacity was associated with adenovirus vectors of non-species C origin, including the ChAdOx1 vaccine platform.

MAIT cell activation augments adenovirus vector vaccine immunogenicity.

Mucosal-associated invariant T (MAIT) cells are innate sensors of viruses and can augment early immune responses and contribute to protection. We hypothesized that MAIT cells may have inherent adjuvant activity in vaccine platforms that use replication-incompetent adenovirus vectors. In mice and humans, ChAdOx1 (chimpanzee adenovirus Ox1) immunization robustly activated MAIT cells. Activation required plasmacytoid dendritic cell (pDC)-derived interferon (IFN)-α and monocyte-derived interleukin-18. IFN-α-induced, monocyte-derived tumor necrosis factor was also identified as a key secondary signal. All three cytokines were required in vitro and in vivo. Activation of MAIT cells positively correlated with vaccine-induced T cell responses in human volunteers and MAIT cell-deficient mice displayed impaired CD8+ T cell responses to multiple vaccine-encoded antigens. Thus, MAIT cells contribute to the immunogenicity of adenovirus vectors, with implications for vaccine design.

In-vitro diagnostic point-of-care tests in paediatric ambulatory care: A systematic review and meta-analysis.

INTRODUCTION: Paediatric consultations form a significant proportion of all consultations in ambulatory care. Point-of-care tests (POCTs) may offer a potential solution to improve clinical outcomes for children by reducing diagnostic uncertainty in acute illness, and streamlining management of chronic diseases. However, their clinical impact in paediatric ambulatory care is unknown. We aimed to describe the clinical impact of all in-vitro diagnostic POCTs on patient outcomes and healthcare processes in paediatric ambulatory care. METHODS: We searched MEDLINE, EMBASE, Pubmed, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science from inception to 29 January 2020 without language restrictions. We included studies of children presenting to ambulatory care settings (general practice, hospital outpatient clinics, or emergency departments, walk-in centres, registered drug shops delivering healthcare) where in-vitro diagnostic POCTs were compared to usual care. We included all quantitative clinical outcome data across all conditions or infection syndromes reporting on the impact of POCTs on clinical care and healthcare processes. Where feasible, we calculated risk ratios (RR) with 95% confidence intervals (CI) by performing meta-analysis using random effects models. RESULTS: We included 35 studies. Data relating to at least one outcome were available for 89,439 children of whom 45,283 had a POCT across six conditions or infection syndromes: malaria (n = 14); non-specific acute fever 'illness' (n = 7); sore throat (n = 5); acute respiratory tract infections (n = 5); HIV (n = 3); and diabetes (n = 1). Outcomes centred around decision-making such as prescription of medications or hospital referral. Pooled estimates showed that malarial-POCTs (Plasmodium falciparum) better targeted antimalarial treatment by reducing over-treatment by a third compared to usual care (RR 0.67; 95% CI [0.58 to 0.77], n = 36,949). HIV-POCTs improved initiating earlier antiretroviral therapy compared to usual care (RR, 3.11; 95% CI [1.55 to 6.25], n = 912). Across the other four conditions, there was limited evidence for the benefit of POCTs in paediatric ambulatory care except for acute respiratory tract infections (RTI) in low-and-middle-income countries (LMICs), where POCT C-Reactive Protein (CRP) may reduce immediate antibiotic prescribing by a third (risk difference, -0.29 [-0.47, -0.11], n = 2,747). This difference was shown in randomised controlled trials in LMICs which included guidance on interpretation of POCT-CRP, specific training or employed a diagnostic algorithm prior to POC testing. CONCLUSION: Overall, there is a paucity of evidence for the use of POCTs in paediatric ambulatory care. POCTs help to target prescribing for children with malaria and HIV. There is emerging evidence that POCT-CRP may better target antibiotic prescribing for children with acute RTIs in LMIC, but not in high-income countries. Research is urgently needed to understand where POCTs are likely to improve clinical outcomes in paediatric settings worldwide.

Typhoidal Salmonella human challenge studies: ethical and practical challenges and considerations for low-resource settings.

Typhoidal Salmonella is a major global problem affecting more than 12 million people annually. Controlled human infection models (CHIMs) in high-resource settings have had an important role in accelerating the development of conjugate vaccines against Salmonella Typhi.The typhoidal Salmonella model has an established safety profile in over 2000 volunteers in high-income settings, and trial protocols, with modification, could be readily transferred to new study sites. To date, a typhoidal Salmonella CHIM has not been conducted in a low-resource setting, although it is being considered.Our article describes the challenges posed by a typhoidal Salmonella CHIM in the high-resource setting of Oxford and explores considerations for an endemic setting.Development of CHIMs in endemic settings is scientifically justifiable as it remains unclear whether findings from challenge studies performed in high-resource non-endemic settings can be extrapolated to endemic settings, where the burden of invasive Salmonella is highest. Volunteers are likely to differ across a range of important variables such as previous Salmonella exposure, diet, intestinal microbiota, and genetic profile. CHIMs in endemic settings arguably are ethically justifiable as affected communities are more likely to gain benefit from the study. Local training and research capacity may be bolstered.Safety was of primary importance in the Oxford model. Risk of harm to the individual was mitigated by careful inclusion and exclusion criteria; close monitoring with online diary and daily visits; 24/7 on-call staffing; and access to appropriate hospital facilities with capacity for in-patient admission. Risk of harm to the community was mitigated by exclusion of participants with contact with vulnerable persons; stringent hygiene and sanitation precautions; and demonstration of clearance of Salmonella infection from stool following antibiotic treatment.Safety measures should be more stringent in settings where health systems, transport networks, and sanitation are less robust.We compare the following issues between high- and low-resource settings: scientific justification, risk of harm to the individual and community, benefits to the individual and community, participant understanding, compensation, and regulatory requirements.We conclude that, with careful consideration of country-specific ethical and practical issues, a typhoidal Salmonella CHIM in an endemic setting is possible.